► Basal cell carcinoma is the most common skin cancer. It presents a local growth with little capacity of dissemination, which implies an important morbidity. Its…
(more)

▼ Basal cell carcinoma is the most common skin cancer. It presents a local growth with little capacity of dissemination, which implies an important morbidity. Its high incidence cause an important demand for health care, which generates high health costs. The therapeutic management of this type of tumour varies according to the characteristics of the patient (age, comorbidities, treatments and preferences) and of the lesion (subtype, size and location). Its therapeutic management in the localized cases is based on the application of invasive therapies (conventional or micrographic surgery) and non-invasive (radiotherapy, photodynamic therapy, cryotherapy or imiquimod). Currently surgery is considered the first treatment option followed by radiation therapy.
Radiotherapy has been used for radical purposes, adjuvants or palliatives, and different techniques may be used depending on the tumour characteristics and the availability of each centre. Despite the great burden of care derived from its management and treatment, there are very few prospective studies of quality that evaluate the different types of radiotherapy in basal cell carcinoma.
New electronic brachytherapy equipment has recently appeared on the market. It is a type of contact radiotherapy that uses X-ray sources. Because of its recent incorporation there is very little clinical information on its implementation, efficacy and safety in the treatment of basal cell carcinoma. On this basis we designed a prospective unicentric pilot study to treat with electronic brachytherapy a limited number of patients with basal cell carcinoma with non-invasive subtypes (superficial and nodular). In total we included 40 patients with 60 lesions in two consecutive groups of 20 patients with two different treatment doses: 36.6 and 42 Gy. We evaluated the efficacy, toxicity and cosmetic results with a follow-ups at 6 months, 1 year and 2 years after treatment. We also performed two sub-studies to determine the role of high frequency cutaneous ultrasound in the determination of tumour depth and the use of dermoscopy in lateral margin delimitation. We obtained good efficacy results, with complete responses above 95% with a two-year follow-up. The toxicity was mild and transient and the cosmetic results were good or excellent in all cases. Although we did not find statistically significant differences in depth determination with ultrasound compared to biopsy, we thought it was a useful technique to define margins. Finally, dermoscopy was useful for delimiting the lateral margin prior to treatment with radiotherapy.
Advisors/Committee Members: Botella Estrada, Rafael, Pérez Calatayud, José, Departament de Medicina.

► Basal cell carcinoma is the most common skin cancer. It presents a local growth with little capacity of dissemination, which implies an important morbidity. Its…
(more)

▼ Basal cell carcinoma is the most common skin cancer. It presents a local growth with little capacity of dissemination, which implies an important morbidity. Its high incidence cause an important demand for health care, which generates high health costs. The therapeutic management of this type of tumour varies according to the characteristics of the patient (age, comorbidities, treatments and preferences) and of the lesion (subtype, size and location). Its therapeutic management in the localized cases is based on the application of invasive therapies (conventional or micrographic surgery) and non-invasive (radiotherapy, photodynamic therapy, cryotherapy or imiquimod). Currently surgery is considered the first treatment option followed by radiation therapy.
Radiotherapy has been used for radical purposes, adjuvants or palliatives, and different techniques may be used depending on the tumour characteristics and the availability of each centre. Despite the great burden of care derived from its management and treatment, there are very few prospective studies of quality that evaluate the different types of radiotherapy in basal cell carcinoma.
New electronic brachytherapy equipment has recently appeared on the market. It is a type of contact radiotherapy that uses X-ray sources. Because of its recent incorporation there is very little clinical information on its implementation, efficacy and safety in the treatment of basal cell carcinoma. On this basis we designed a prospective unicentric pilot study to treat with electronic brachytherapy a limited number of patients with basal cell carcinoma with non-invasive subtypes (superficial and nodular). In total we included 40 patients with 60 lesions in two consecutive groups of 20 patients with two different treatment doses: 36.6 and 42 Gy. We evaluated the efficacy, toxicity and cosmetic results with a follow-ups at 6 months, 1 year and 2 years after treatment. We also performed two sub-studies to determine the role of high frequency cutaneous ultrasound in the determination of tumour depth and the use of dermoscopy in lateral margin delimitation. We obtained good efficacy results, with complete responses above 95% with a two-year follow-up. The toxicity was mild and transient and the cosmetic results were good or excellent in all cases. Although we did not find statistically significant differences in depth determination with ultrasound compared to biopsy, we thought it was a useful technique to define margins. Finally, dermoscopy was useful for delimiting the lateral margin prior to treatment with radiotherapy.
Advisors/Committee Members: Botella Estrada, Rafael, Pérez Calatayud, José, Departament de Medicina.

▼ Complex intensity modulated fields delivered by means of rotational dynamic techniques, such as Volumetric Modulated Arc Therapy (VMAT), can be considered a step forward in comparison to conventional, static technique, providing demanding dose distributions in short irradiation times. However this dynamic implementation involves two main sources of uncertainty: one related to the dose calculation accuracy, and the other linked to the continuous delivery of a discrete calculation. Therefore, require new quality assurance (QA) protocols and detailed verification capable of predicting the actual delivered dose to the patient. This is especially critical when used with hypofractionated schemes and for stereotactic body radiotherapy (SBRT) treatments. In this scenario, Monte Carlo (MC) simulation presents an ideal tool to complete the linac commissioning required for VMAT, as well as the gold standard for dose distribution verification.
The present thesis reflects the work carried out in order to implement a routine MC verification of VMAT treatments, and to develop a QA model able to control and potentially reduce the inherent uncertainties for a fair and reliable evaluation of current VMAT solutions, including further evaluation of VMAT QA systems. The developed model consists on a system composed by a specific phantom integrated with MC simulation of VMAT log files in a feedback procedure by implementing an optimization process able to adjust the Monitor Units and reconstruct the dose-volume histogram on the patient CT.
Several clinical cases, previously planned with different treatment planning systems and verified with different commercial solutions were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements. The proposed model showed to be valid for VMAT assessment, and also for linac commissioning and evaluation of other QA systems. Besides, the results also showed enough robustness and efficiency of the model to be considered as a pre-treatment VMAT verification system.
Advisors/Committee Members: Leal Plaza, Antonio (advisor), Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica (affiliation), Universidad de Sevilla. CTS-233 Fisica Medica (group).

► The induction of secondary cancer as a consequence of the radiotherapy treatment is an issue of concern nowadays. This fact makes relevant to consider all…
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▼ The induction of secondary cancer as a consequence of the radiotherapy treatment is an issue of concern nowadays. This fact makes relevant to consider all the dose delivered to the patient and, thus, it is necessary to include the peripheral dose. In this work we focused on the neutron radiation generated by high energy (i.e. > 10 MV) photon radiotherapy beams given that the accurate determination of the neutron equivalent doses is still a challenging task in radiotherapy. This situation is responsible of the fact that, in the implementation of modern techniques (such as intensity modulated radiotherapy), a blind choice has to be done between low energies (i.e., 6MV) (with no neutrons but throwing away the potential benefit of better conformality) and high energies (with the subsequent secondary cancer risk associated to neutrons).
The aim of this work was to develop a model for the estimation in real time of neutron equivalent doses and propose a methodology to include the effect of this neutron contamination (through the associated secondary cancer risk or probability) in the evaluation of the radiotherapy treatment success by means of an integral radiobiological approach.
The neutron equivalent dose model is based on the correlation between the readings of a new digital detector, which allows a real time measurement of the neutron production inside the treatment room, and the equivalent doses inside an anthropomorphic phantom for several irradiation conditions. This correlation model has been further extended to estimate neutron equivalent dose at specific organs in patients. Using current risk model
from international organisms, estimation of the secondary cancer risk due to neutrons has been performed. The methodology was applied to 1377 patients in a total of 50 different facilities. Those measurements covered 15 different combinations of linac manufacturer and nominal energy. A data base has been generated with such information. The main result is that equivalent dose and secondary cancer probability scale with the number of monitor units (MU). Thus, a procedure has been established in order to makes estimates of both magnitudes from the number of MU of any treatment. This enables a quick estimation of cancer risk during treatment planning.
The selection of the best radiotherapy treatment strategy is starting to routinely involve the evaluation of dose distributions in terms of the radiobiological response of tissues through the application of tumour control and normal tissue complication probabilities functions. In this work, it is proposed that secondary cancer probability can be included as an extra complication term. Thus, a new function, termed Uncomplicated and Cancer-Free tumour Control Probability has been defined representing a biologic objective function which estimates the probability to achieve complication-free tumour control, without cancer induction. This function was applied to a selected prostate case planned with all available radiotherapy treatment strategies. The results of this…
Advisors/Committee Members: Sánchez Doblado, Francisco (advisor), Sánchez Nieto, Beatriz (advisor), Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica (affiliation).

► A study is made of the alterations induced by ionizing radiation upon the accessory salivary glands of the lips in a series of 17 patients…
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▼ A study is made of the alterations induced by ionizing radiation upon the
accessory salivary glands of the lips in a series of 17 patients with malignant
head and neck tumors programmed for radiotherapy encompassing the region
of the lips.
Salivary secretion was evaluated, along with the morphological alterations of
the glands at the time of diagnosis and three months after the completion of
radiotherapy.
Prior to radiotherapy, mean salivary secretion was 0.21 ml/min., and four
patients had mild gland atrophy. Three months after radiotherapy, mean
salivary secretion decreased to 0.05 ml/min., and all patients showed gland
atrophy (mild in 7, moderate in 7 and severe in 3 cases).
Patients subjected to radiotherapy encompassing the lips within the
irradiated field show diminished salivary flow, manifesting as xerostomia. The
associated morphological changes comprise gland atrophy, with a reduction in
the number of acini, duct dilatation, and fibroadipose replacement of the
periglandular connective tissue.
Advisors/Committee Members: Bagán Sebastián, José Vicente, Basterra Alegría, Jorge, Universitat de València - CIRURGIA.

► A study is made of the alterations induced by ionizing radiation upon the accessory salivary glands of the lips in a series of 17 patients…
(more)

▼ A study is made of the alterations induced by ionizing radiation upon the
accessory salivary glands of the lips in a series of 17 patients with malignant
head and neck tumors programmed for radiotherapy encompassing the region
of the lips.
Salivary secretion was evaluated, along with the morphological alterations of
the glands at the time of diagnosis and three months after the completion of
radiotherapy.
Prior to radiotherapy, mean salivary secretion was 0.21 ml/min., and four
patients had mild gland atrophy. Three months after radiotherapy, mean
salivary secretion decreased to 0.05 ml/min., and all patients showed gland
atrophy (mild in 7, moderate in 7 and severe in 3 cases).
Patients subjected to radiotherapy encompassing the lips within the
irradiated field show diminished salivary flow, manifesting as xerostomia. The
associated morphological changes comprise gland atrophy, with a reduction in
the number of acini, duct dilatation, and fibroadipose replacement of the
periglandular connective tissue.
Advisors/Committee Members: Bagán Sebastián, José Vicente, Basterra Alegría, Jorge, Universitat de València - CIRURGIA.